The kallikrein-kinin system (KKS) is an intricate phenomenon that has evolved to demonstrate wide distribution through all the systems of the body. For instance, blood has a unique kallikrein (PKa) with reported involvement in inflammation and coagulation, the brain has the tissue kallikrein (KLK 1), the prostate has the human glandular KLK 3, the skin has multiple tissue KLKs including KLK 5, KLK 6, and KLK 7. PKa mediated generation of activated factor XII (Hageman Factor) and subsequent proteolytic coagulation cascade activation also determine the final thrombus quality by contributing to the stability of the clot structure within the thrombus. Dysregulation of plasma KKS expression is associated with many inflammatory diseases including hereditary angioedema. In contrast, tissue KKS are ubiquitous constituents of tissues, essential in operating as a proteolytic cascade within the tissue. This system is mainly composed of 15 different genes encoding a family of 15 proteases. The KLKs are serine proteases exhibiting trypsin- or chymotrypsin-like activities and sharing important structural and functional properties. The KLK 1, through a proteolytic cleavage, liberates kinin from low molecular weight kininogen. Both PKa and KLK 5 are capable of generating plasmin, highlighting their importance in the remodeling of the fibrin clot during wound healing. Dysregulation of tissue KLK expression is associated with many inflammatory diseases and cancer types, such as prostate or ovarian cancer.
This Research Topic analyzes and discusses the large and growing complexity of both plasma PKa and the proteolytic activation cascade of tissue KLKs. With this Topic we aim to analyze the results of comparative genomic studies that have provided a highly detailed view of how KLKs and PKa are related to each other at the genetic level. Both the plasma and tissue KKS have powerful interactions with inflammation, which negatively influences numerous physiological functions, causing an array of diseases including diabetes, cancer, cardiovascular, and neurodegenerative diseases; and aging. This Research Topic analyzes biological, physiological, immunological, pharmacological, and clinical perspectives, and how the PKa and KLKs impact each other under inflammatory conditions and cancer. The levels of KLKs complexity and mechanisms of KLKs regulation will then be addressed and used in ways to further our understanding of KKS and inflammatory processes.
This Research Topic aims to discuss current frontiers and future perspectives in both plasma and tissue KKS research. We encourage the submission of articles that report development or application of novel drugs relevant to PKa and KLKs, and pharmacologically active kinins. An historical approach about plasma and tissue KKS and kinins derivative peptides is also encouraged. Moreover, a transdisciplinary approach can explain the importance of the combined effects of PKa and KLK1 in the inflammatory phase, and the discrepancy in opinion towards them. Lastly, we are also interested in elucidating the role of the KKS in the onset and pathophysiology of COVID-19.
The kallikrein-kinin system (KKS) is an intricate phenomenon that has evolved to demonstrate wide distribution through all the systems of the body. For instance, blood has a unique kallikrein (PKa) with reported involvement in inflammation and coagulation, the brain has the tissue kallikrein (KLK 1), the prostate has the human glandular KLK 3, the skin has multiple tissue KLKs including KLK 5, KLK 6, and KLK 7. PKa mediated generation of activated factor XII (Hageman Factor) and subsequent proteolytic coagulation cascade activation also determine the final thrombus quality by contributing to the stability of the clot structure within the thrombus. Dysregulation of plasma KKS expression is associated with many inflammatory diseases including hereditary angioedema. In contrast, tissue KKS are ubiquitous constituents of tissues, essential in operating as a proteolytic cascade within the tissue. This system is mainly composed of 15 different genes encoding a family of 15 proteases. The KLKs are serine proteases exhibiting trypsin- or chymotrypsin-like activities and sharing important structural and functional properties. The KLK 1, through a proteolytic cleavage, liberates kinin from low molecular weight kininogen. Both PKa and KLK 5 are capable of generating plasmin, highlighting their importance in the remodeling of the fibrin clot during wound healing. Dysregulation of tissue KLK expression is associated with many inflammatory diseases and cancer types, such as prostate or ovarian cancer.
This Research Topic analyzes and discusses the large and growing complexity of both plasma PKa and the proteolytic activation cascade of tissue KLKs. With this Topic we aim to analyze the results of comparative genomic studies that have provided a highly detailed view of how KLKs and PKa are related to each other at the genetic level. Both the plasma and tissue KKS have powerful interactions with inflammation, which negatively influences numerous physiological functions, causing an array of diseases including diabetes, cancer, cardiovascular, and neurodegenerative diseases; and aging. This Research Topic analyzes biological, physiological, immunological, pharmacological, and clinical perspectives, and how the PKa and KLKs impact each other under inflammatory conditions and cancer. The levels of KLKs complexity and mechanisms of KLKs regulation will then be addressed and used in ways to further our understanding of KKS and inflammatory processes.
This Research Topic aims to discuss current frontiers and future perspectives in both plasma and tissue KKS research. We encourage the submission of articles that report development or application of novel drugs relevant to PKa and KLKs, and pharmacologically active kinins. An historical approach about plasma and tissue KKS and kinins derivative peptides is also encouraged. Moreover, a transdisciplinary approach can explain the importance of the combined effects of PKa and KLK1 in the inflammatory phase, and the discrepancy in opinion towards them. Lastly, we are also interested in elucidating the role of the KKS in the onset and pathophysiology of COVID-19.